The long term goal of this research program is to improve care of patients harboring cerebral (brain) aneurysms by combining genetic and tissue engineering with modern medical device technology. Cerebral aneurysms represent an important clinical problem, with rupture-induced morbidity and mortality affecting 30,000 patients per year in the US. The need for highly invasive, open brain surgery for treatment of such aneurysms has been partially reduced by development of platinum microcoils; these coils can be placed through small, flexible microcatheters into brain aneurysms, avoiding open surgery. Unfortunately, these microcoils fail to induce in vivo cellular proliferation and matrix deposition that would lead to permanent occlusion of aneurysms. Regrowth of aneurysms after microcoil therapy remains common with current technologies. In this proposal we will address this important clinical problem through a genetic and tissue engineering approach. We will enhance the ability of microcoils to induce cellular proliferation within aneurysm cavities by using such coils as carriers of fibroblast allografts. Further, through in vitro gene transfer techniques, we will enhance the ability of implanted cellular allografts to synthesize and secrete collagen, which will serve to reinforce the aneurysm cavity. Last, we will improve this genetic and tissue engineering approach to aneurysm therapy by use of new, minimally inflammatory "empty" adenoviruses. Our research program cross-cuts basic science and technology and represents a highly focused approach aimed at a persistent, well-defined clinical problem. Successful implementation of this research program will advance the field of genetic and tissue engineering and will improve the care of patients harboring life-threatening cerebral aneurysms.